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Cardiac Hormone Replacement With Brain Natriuretic Peptide (BNP) in Heart Failure (SubqBNP)

Primary Purpose

Congestive Heart Failure, Cardiomyopathy

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
B-type Natriuretic Peptide (BNP)
Placebo
Sponsored by
Horng Chen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Congestive Heart Failure focused on measuring Heart failure, Natriuretic peptides, B-type natriuretic peptide, Kidney, Nesiritide, Natrecor, CHF

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age > 18 years Resting left ventricular ejection fraction (LVEF) of 35% or less (determined within 48 months of recruitment by echocardiography, multiple gate acquisition scan (MUGA) or left ventriculogram.) New York Heart Association (NYHA) Class I (with previous symptoms of heart failure), Class II and III Female subjects not menopausal or surgically sterilized will need to have a negative pregnancy test the day before the study day and be on contraception. Exclusion Criteria: Myocardial infarction (MI) within 3 months of screening. Unstable angina within 14 days of screening, or any evidence of myocardial ischemia. Valvular stenosis, hypertrophic, restrictive or obstructive cardiomyopathy, constrictive pericarditis, primary pulmonary hypertension, or biopsy proven active myocarditis. Sustained ventricular tachycardia (VT) or ventricular fibrillation (V-fib) within 14 days of screening. Second or third degree atrioventricular (AV) block without a permanent cardiac pacemaker. Cerebrovascular accident (CVA) within 3 months of screening, or other evidence of significantly compromised central nervous system (CNS) perfusion. Serum creatinine of >3.0 mg/dL. Serum sodium of <125 milliequivalents per decaLiter (mEq/dL) or > 160 mEq/dL. Serum potassium of < 3.5 mEq/dL or > 5.2 mEq/dL. Serum digoxin level of > 2.0 ng/ml. Systolic pressure of <85 mmHg immediately prior to the first injection of study drug/placebo. LVEF > 35% by within 24 months of screening. Unable to self-administer subcutaneous injection twice a day. Diagnosed with AIDS or known positive HIV titer. Other acute or chronic medical conditions or laboratory abnormality, which may increase the risks, associated with study participation or may interfere with interpretation of the data. Received an investigational drug within 1 month prior to dosing. Unable to undergo cardiac magnetic resonance imaging (MRI). Contraindications to MRI include pacemaker or defibrillator, pregnant women, atrial fibrillation or other arrhythmia, cerebral aneurysm clips, or severe claustrophobia. In the opinion of the investigator, is unlikely to comply with the study protocol or is unsuitable for any reasons. Patient in atrial fibrillation or who have a pacemaker or implantable cardioverter defibrillator (ICD) Hemoglobin < 10g/dl. Patients with an allergy to iodine.

Sites / Locations

  • Mayo Clinic

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

B-type Natriuretic Peptide (BNP)

Placebo

Arm Description

BNP (nesiritide) administered subcutaneously twice daily for 8 weeks at 10 mcg/kg.

Placebo self-administered subcutaneously twice daily for 8 weeks.

Outcomes

Primary Outcome Measures

Change in Left Ventricular (LV) Volume Index at 8 Weeks
LV volume was measured for systolic volume and diastolic volume using a cardiac Magnetic Resonance Imaging (MRI) scan. All cardiac MRI images were reviewed by an independent cardiologist in a blinded fashion.
Change in Left Ventricular (LV) Mass Index at 8 Weeks

Secondary Outcome Measures

Change in Left Ventricular (LV) Filling Pressure at 8 Weeks
Filling pressure determined by ratio of E/e' [Echocardiograph Doppler mitral inflow velocity (E) to mitral annulus tissue Doppler velocity (e') ratio]
Change in Plasma Renin Activity at 8 Weeks
Plasma renin is synthesized within circulation or at tissue sites, causing vasoconstriction or vasodilation.
Change in Renal Function as Measured by Glomerular Filtration Rate (GFR) at 8 Weeks
Kidney function was measured by GFR determined by iothalamate clearance. Glomerular filtration rate describes the flow rate of filtered fluid through the kidney measured in milliliters per minute per 1.73 m^2 of body-surface area. A lower GFR means the kidney is not filtering normally.
Change in Heart Rate at 8 Weeks
Heart rate was measured when MRI was performed
Change in Blood Pressure at 8 Weeks
Blood pressure was measured during the MRI
Change in Left Ventricular Ejection Fraction at 8 Weeks
Left Ventricle Ejection Fraction (LVEF)is a clinical parameter used by cardiologists to describe how well the heart is pumping. LVEF is a measure of the amount of blood pumped out of the lower chamber (ventricle) of the heart during a heartbeat, measured by Magnetic Resonance Imaging (MRI).

Full Information

First Posted
November 10, 2005
Last Updated
December 19, 2012
Sponsor
Horng Chen
Collaborators
American Heart Association, Scios, Inc., National Heart, Lung, and Blood Institute (NHLBI), National Center for Research Resources (NCRR)
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1. Study Identification

Unique Protocol Identification Number
NCT00252187
Brief Title
Cardiac Hormone Replacement With Brain Natriuretic Peptide (BNP) in Heart Failure
Acronym
SubqBNP
Official Title
Cardiac Hormone Replacement With BNP in Heart Failure: A Novel Therapeutic Strategy
Study Type
Interventional

2. Study Status

Record Verification Date
December 2012
Overall Recruitment Status
Completed
Study Start Date
January 2000 (undefined)
Primary Completion Date
July 2008 (Actual)
Study Completion Date
June 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Horng Chen
Collaborators
American Heart Association, Scios, Inc., National Heart, Lung, and Blood Institute (NHLBI), National Center for Research Resources (NCRR)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to determine the effects of subcutaneous injection of Human BNP (nesiritide), a hormone produced by the heart, on the pumping ability of the heart, kidney function, and hormonal function in persons with heart failure.
Detailed Description
The cardiac hormone brain natriuretic peptide (BNP) plays an important role in the pathophysiology of congestive heart failure (CHF). Studies have established that BNP mediates natriuresis, renin and aldosterone (RAAS) inhibition, vasodilation and lusitropism. Acute cardiac hormone replacement with intravenous infusion of BNP has been shown to possess potent vasodilating actions in humans with acute decompensated CHF resulting in improvement of clinical symptoms. Natrecor (nesiritide) a sterile, purified preparation of human BNP is approved by the FDA for intravenous administration in the treatment of patients with acute decompensated congestive heart failure. However, chronic cardiac hormone replacement with BNP as therapeutic strategy in CHF has been limited by the need to administer BNP intravenously. The objective of this study is to define the cardiorenal and humoral actions of short term (eight weeks) chronic cardiac hormone replacement with subcutaneous (SQ) BNP in human NYHA class II-III CHF. Systolic and diastolic function, left ventricular remodeling as assessed by its volume, renal function, neurohumoral profiling and exercise capacity will be assessed prior to and after eight weeks of treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Congestive Heart Failure, Cardiomyopathy
Keywords
Heart failure, Natriuretic peptides, B-type natriuretic peptide, Kidney, Nesiritide, Natrecor, CHF

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
45 (Actual)

8. Arms, Groups, and Interventions

Arm Title
B-type Natriuretic Peptide (BNP)
Arm Type
Active Comparator
Arm Description
BNP (nesiritide) administered subcutaneously twice daily for 8 weeks at 10 mcg/kg.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo self-administered subcutaneously twice daily for 8 weeks.
Intervention Type
Drug
Intervention Name(s)
B-type Natriuretic Peptide (BNP)
Other Intervention Name(s)
Nesiritide
Intervention Description
BNP hormone self-administered subcutaneously twice daily for 8 weeks at 10 mcg/kg.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo self-administered subcutaneously twice daily for 8 weeks.
Primary Outcome Measure Information:
Title
Change in Left Ventricular (LV) Volume Index at 8 Weeks
Description
LV volume was measured for systolic volume and diastolic volume using a cardiac Magnetic Resonance Imaging (MRI) scan. All cardiac MRI images were reviewed by an independent cardiologist in a blinded fashion.
Time Frame
Baseline and 8 weeks
Title
Change in Left Ventricular (LV) Mass Index at 8 Weeks
Time Frame
Baseline and 8 weeks
Secondary Outcome Measure Information:
Title
Change in Left Ventricular (LV) Filling Pressure at 8 Weeks
Description
Filling pressure determined by ratio of E/e' [Echocardiograph Doppler mitral inflow velocity (E) to mitral annulus tissue Doppler velocity (e') ratio]
Time Frame
Baseline and 8 weeks
Title
Change in Plasma Renin Activity at 8 Weeks
Description
Plasma renin is synthesized within circulation or at tissue sites, causing vasoconstriction or vasodilation.
Time Frame
Baseline and 8 weeks
Title
Change in Renal Function as Measured by Glomerular Filtration Rate (GFR) at 8 Weeks
Description
Kidney function was measured by GFR determined by iothalamate clearance. Glomerular filtration rate describes the flow rate of filtered fluid through the kidney measured in milliliters per minute per 1.73 m^2 of body-surface area. A lower GFR means the kidney is not filtering normally.
Time Frame
Baseline and 8 weeks
Title
Change in Heart Rate at 8 Weeks
Description
Heart rate was measured when MRI was performed
Time Frame
Baseline and 8 weeks
Title
Change in Blood Pressure at 8 Weeks
Description
Blood pressure was measured during the MRI
Time Frame
Baseline and 8 weeks
Title
Change in Left Ventricular Ejection Fraction at 8 Weeks
Description
Left Ventricle Ejection Fraction (LVEF)is a clinical parameter used by cardiologists to describe how well the heart is pumping. LVEF is a measure of the amount of blood pumped out of the lower chamber (ventricle) of the heart during a heartbeat, measured by Magnetic Resonance Imaging (MRI).
Time Frame
Baseline and 8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age > 18 years Resting left ventricular ejection fraction (LVEF) of 35% or less (determined within 48 months of recruitment by echocardiography, multiple gate acquisition scan (MUGA) or left ventriculogram.) New York Heart Association (NYHA) Class I (with previous symptoms of heart failure), Class II and III Female subjects not menopausal or surgically sterilized will need to have a negative pregnancy test the day before the study day and be on contraception. Exclusion Criteria: Myocardial infarction (MI) within 3 months of screening. Unstable angina within 14 days of screening, or any evidence of myocardial ischemia. Valvular stenosis, hypertrophic, restrictive or obstructive cardiomyopathy, constrictive pericarditis, primary pulmonary hypertension, or biopsy proven active myocarditis. Sustained ventricular tachycardia (VT) or ventricular fibrillation (V-fib) within 14 days of screening. Second or third degree atrioventricular (AV) block without a permanent cardiac pacemaker. Cerebrovascular accident (CVA) within 3 months of screening, or other evidence of significantly compromised central nervous system (CNS) perfusion. Serum creatinine of >3.0 mg/dL. Serum sodium of <125 milliequivalents per decaLiter (mEq/dL) or > 160 mEq/dL. Serum potassium of < 3.5 mEq/dL or > 5.2 mEq/dL. Serum digoxin level of > 2.0 ng/ml. Systolic pressure of <85 mmHg immediately prior to the first injection of study drug/placebo. LVEF > 35% by within 24 months of screening. Unable to self-administer subcutaneous injection twice a day. Diagnosed with AIDS or known positive HIV titer. Other acute or chronic medical conditions or laboratory abnormality, which may increase the risks, associated with study participation or may interfere with interpretation of the data. Received an investigational drug within 1 month prior to dosing. Unable to undergo cardiac magnetic resonance imaging (MRI). Contraindications to MRI include pacemaker or defibrillator, pregnant women, atrial fibrillation or other arrhythmia, cerebral aneurysm clips, or severe claustrophobia. In the opinion of the investigator, is unlikely to comply with the study protocol or is unsuitable for any reasons. Patient in atrial fibrillation or who have a pacemaker or implantable cardioverter defibrillator (ICD) Hemoglobin < 10g/dl. Patients with an allergy to iodine.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Horng H. Chen, M.D.
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
23122795
Citation
Chen HH, Glockner JF, Schirger JA, Cataliotti A, Redfield MM, Burnett JC Jr. Novel protein therapeutics for systolic heart failure: chronic subcutaneous B-type natriuretic peptide. J Am Coll Cardiol. 2012 Dec 4;60(22):2305-12. doi: 10.1016/j.jacc.2012.07.056. Epub 2012 Nov 1.
Results Reference
derived
Links:
URL
http://clinicaltrials.mayo.edu
Description
Mayo Clinic Clinical Trials

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Cardiac Hormone Replacement With Brain Natriuretic Peptide (BNP) in Heart Failure

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